Clinical and pathological evidence suggest the existence of a diabetic cardiomyopathy in man. Studies of myocardial function in experimental diabetes have been limited. Work done in this laboratory has shown that severe diabetes in rats results in the development of significant alterations in the mechanical performance of left ventricular papillary muscle, including a major slowing of relaxation and a depression in shortening velocity. These changes occur within one month of the onset of diabetes and are stable over a six month period. Changes in actomyosin ATPase and sarcoplasmic reticulum uptake of calcium were observed, providing a basis for the observed mechanical alterations. The proposed study will further characterize myocardial function in the diabetic rat. The effects of less severe diabetes will be examined. The effect of insulin therapy on cardiac tissue will be analyzed, with consideration given to the influence of both the duration of therapy and the degree of control of blood glucose. The effect of diabetes on cardiac muscle function in the rabbit, a mammalian species whose mechanisms of excitation/contraction coupling and relaxation differ from the rat, will be studied. Studies of myocardial function in several models of experimental diabetes will clarify the existence of a diabetic cardiomyopathy, elucidate its mechanisms and provide knowledge of the effects of therapy.